Fisetin suppresses 1,2-dimethylhydrazine-induced colon tumorigenesis in Wistar rats

Abstract The present research exploration is intended to inspect the chemotherapeutic potency of fisetin in 1,2‑dimethylhydrazine (DMH)-stimulated colon carcinoma in Wistar rats. The 20mg/kgb.wt of DMH was injected to the investigational rats via subcutaneous route once in a week for 15 weeks to induce colon cancer in a rat model. Fisetin at 50mg/kgb.wt dose were administered throughout the experimental period. Biochemical methods were employed to study the antioxidant, lipid peroxidation, Phase-I & II enzymes. Pro-inflammatory cytokines and apoptotic proteins were measured using Elisa methods. Colon tissue damages were examined using hematoxylin and eosin staining. Our result suggested that fisetin treatment efficiently decreased the tumor incidence andnumber by restoring the antioxidant status, phase-II enzymes and inhibiting the actions of phase-I enzymes and lipid peroxidative events in DMH-induced colon tumorigenesis model. Further, we noticed that fisetin treatment significantly inhibited the pro-inflammatory cytokine production. Moreover, we observed that fisetin treatment remarkably inhibited the anti-apoptotic Bcl-2 and induced pro-apoptotic Caspase-9 and Caspase-3 expression, thereby induces apoptosis in DMH-induced colon tumorigenesis model. From this observation, we conclude that fisetin (50mg/kgb.wt) can efficiently prevent chemically induced colon cancer by enhancing antioxidant status and modulating inflammatory and apoptotic signalling events.